One of the leading areas of antibody research is bispecific antibodies. The Sixth Annual Advancing Bispecific Antibodies and Combination Therapy to the Clinic meeting will showcase leaders sharing clinical and preclinical outcomes on a variety of
bispecific and multi-specific constructs. The creation of novel formats and combination therapy is yielding very exciting results and this meeting will highlight progress and assess safety, manufacturing and developability concerns.
Scientific Advisory Board
Frank Comer, PhD, Scientist, MedImmune
Rakesh Dixit, PhD, DABT, Vice President, R & D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
Robert Mabry, PhD, Vice President, Protein Science. Cogen Therapeutics, Inc.
Final Agenda
SC9: CAR T Cell Therapy for Solid Tumors
*Separate registration required.
WEDNESDAY, MAY 2
7:30 am Registration(Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Remarks
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
8:40 Introduction and Overview of Bispecific Antibodies
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
9:10 Using Oncolytic Viruses to Deploy Bispecific Antibodies for Targeted Cancer Therapy
Leonard Seymour, PhD, Professor, Gene Therapy, Oncology, University of Oxford
Oncolytic viruses replicate selectively within tumor cells and lyse them before spreading to infect other cells. We have ‘armed’ an oncolytic group B adenovirus to encode bispecific T cell engagers (BiTEs) and express them selectively
within tumor cells, secreting them into the tumour microenvironment. In this way we can activate tumor-associated T cells to attack cancer cells (or cancer stromal cells) by judicious choice of BiTE specificity, whilst simultaneously avoiding
any delivery-related systemic toxicities.
9:40 Bispecifics to the Rescue: Reviving Exhausted T Cells with Dual Costimulation
Raphael Clynes, MD, PhD, Vice President, Translational Biology, Xencor, Inc.
To improve therapeutic efficacy of single agent checkpoint blockade, engagement of multiple inhibitory receptors and/or agonist receptors offers the possibility to more robustly reinvigorate exhausted intratumoral T cells. Bispecific antibodies
offer the potential to accomplish this with both enhanced selectivity and avidity for exhausted T cells, improving both on-target efficacy and limit off-target immunotoxicity. We will present the preclinical rationale for three bispecific
antibodies anticipated to enter the clinic in 2018, including an anti-PD1/anti-CTLA4, an anti-CTLA-4/anti-LAG3, and an anti-PD1/anti-ICOS.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
10:55 Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment
Dirk Hose, PhD, Priv.-Doz. Dr. med. Dr. biol. hom., Head, Multiple Myeloma Research Laboratory, Universitaetsklinikum Heidelberg,
Medizinische Klinik V
B-cell-maturation antigen (BCMA) is a TCB-target expressed in all malignant plasma-cell samples at RNA (n=726) and protein (n=43) level, as on normal plasma-cells. The BCMA-TCB EM801 shows efficacy in 34/43 (79%) primary MM-patients’
BM-samples, a H929-xenograft reconstituted NOG-mouse-model, and cynomolgus monkeys. EM801 kills malignant plasma-cells by coupling them with T-cells, inducing T-cell-activation, secretion of e.g. interferon-γ, granzyme B and perforin.
The higher affinity derivative EM901 (CC-93269) is foreseen entering clinical phase I/II trials.
11:25 The Promise and Challenge of T-Cell-Redirecting Bispecific Antibodies Made by the DNL Platform
Chien-Hsing Ken Chang, PhD, Vice President, Research & Development, Immunomedics, Inc.
Accumulating evidence has indicated the antitumor immunity of T cells induced upon ligation with a bsAb to target tumor cells also incurs a concurrent activation of various cell-bound as well as -secreted factors to promote tumor growth. Elucidating
the relative contribution of each of these factors to the destruction and protection of tumor presents a challenge, and provides insights into selecting optimal combination therapy with T cells redirected by bsAbs.
11:55 Engineering High Affinity Tetravalent Bispecific Immune Cell Engagers to Destroy Malignant Cells with Low Target Expression
Michael Tesar, PhD, Research Program Head, Research and Development, Affimed GmbH
Affimed is a leader in NK cell directed therapies and its tetravalent bispecific immune cell engager platform utilizes a unique mode of action. Newest developments from our clinical and preclinical programs will be presented.
12:25
pm IGM-2323: A Potent, High Avidity IgM Bi-Specific Anti-CD20xCD3 Antibody with Longer Half-Life and Increased Safety
Ramesh Baliga, PhD, Vice President, Discovery Biology, IGM Biosciences, Inc.
12:55 LUNCHEON PRESENTATION I: A Novel Phenotypic Approach for Predicting Tumor Response
Mark Paris, PhD, Associate Director, Translational Applications, Mitra Biotech
1:25 Luncheon Presentation II: Developing First-In-Class Immune Cell Engagers for the Activation of Innate and Adaptive Immunity to Fight Cancer
Martin Treder, PhD, CSO, Affimed
1:55 Session Break
2:10 Chairperson’s Remarks
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
2:15 PANEL DISCUSSION: Bispecific Oncology Biologics Efficacy and Safety: Do the Platforms of Bispecifics Matter?
Moderator:
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
Panelists:
Jennifer F. Nemeth, PhD, SCPM, Director, Biophysics, Structural Characterization, Biologics Discovery Sciences, Janssen Research & Development
Jacintha Shenton, PhD, Scientific Director, Biologics Toxicology, Janssen BioTherapeutics,
Janssen R&D
Raphael Clynes, MD, PhD, Vice President, Translational Biology, Xencor, Inc.
- Challenges of more than 50 bispecific platforms
- Impact of effector function, half-life, bispecific targets (soluble vs. membrane bound antigens)
- Heme vs. non-heme tumors
- CMC, Manufacturing Considerations
3:15 Model Aided Drug Invention Case Studies in Research and Development
John Burke, PhD, Co-Founder, President and CEO, Applied BioMath, LLC
Two studies will be shown that highlight examples of Model Aided Drug Invention (MADI) efforts, which include mechanistic PK/PD and QSP approaches, that accelerated the discovery and development of best-in-class therapeutics and
impacted critical decisions. Examples include: (1) predicting optimal drug properties and differentiation for bispecific biologics vs. fixed dose combinations (FDC) in targeting PD-1 and Tim-3; and (2) predicting optimal drug
properties for a bispecific approach maximizing target coverage in the joint for Osteoarthritis.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:45 Problem-Solving Breakout Discussions (Commonwealth Hall)
Applying CAR Technology Toward a Functional Cure of HIV Infection
Moderator: Edward A. Berger, PhD, Chief, Molecular Structure Section, Laboratory of Viral Diseases, NIAID, National Institutes of Health
- What features of CAR design will help achieve durable (like-long?) suppression of HIV?
- How should CAR gene be introduced (host cell type, mode of gene insertion)?
- What animal models are best suited to test CAR technology against HIV?
- Can a “universal CAR” be developed as alternative to individual-specific treatment?
Bispecifics in The Clinic
Moderator: Raphael Clynes, MD, PhD, Vice President, Translational Biology, Xencor, Inc.
- Lessons on dosing
- Managing toxicities
- Optimizing affinities for targets
- Use of Fc domains
- Target selection in Heme and solid tumors
Treatment of Plasma Cell Diseases with TCB and Combination Treatment
Moderator: Dirk Hose, PhD, Priv.-Doz. Dr. med. Dr. biol. hom. Dirk Hose, Head, Multiple Myeloma Research Laboratory, Universitaetsklinikum Heidelberg, Medizinische Klinik V
- targets
- target related side effects
- combination partners in multiple myeloma and AL-amyloidosis
- timing of TCB treatment – early or late?
- TCB or CAR-T or both?
Oncolytic Viruses for Targeted Cancer Therapy
Moderator: Len Seymour, PhD, Professor, Gene Therapy, Oncology, University of Oxford
- Choice of viral vectors for targeted delivery of bispecifics
- Control of expression of bispecific antibodies
- Selectivity and avoiding off target effects
Coupling a Tumor-Specific ADC Target to a Rapidly Internalizing Protein as an Approach to Enhance Efficacy of ADC
Moderator: Julian Andreev, PhD, Senior Staff Scientist, Oncology and Angiogenesis, Regeneron Pharmaceuticals
- Which “rapidly internalizing proteins” can be successfully used in this approach?
- What are the best targets for this approach?
- What are the pitfalls of the approach?
5:45 Networking Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:00 End of Day
THURSDAY, MAY 3
8:00 am Registration(Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Remarks
Frank Comer, PhD, Scientist, MedImmune
David D. Ho, MD, Aaron Diamond AIDS Research Center, The Rockefeller University
The plasticity of HIV-1 demands additional improvements to these mAbs to better ensure their clinical utility. This talk will discuss engineered bispecific antibodies that are the most potent and broad HIV-neutralizing antibodies
to date such as 10E8V2.0/iMab which reduced virus load substantially in HIV-1-infected humanized mice and also provided complete protection when administered prior to virus challenge. These bispecific antibodies hold promise
as novel prophylactic and/or therapeutic agents in the fight against HIV-1.
9:05 Bispecific Antibodies and Antibody–Drug Conjugates (ADCs) Bridging HER2 and Prolactin Receptor Improve Efficacy of HER2 ADCs
Julian Andreev, PhD, Senior Staff Scientist, Oncology and Angiogenesis, Regeneron Pharmaceuticals
There is a need for HER2-directed ADCs effective in patients expressing low/moderate levels of HER2. Cross-linking HER2 to constitutively internalizing PRLR, using a HER2xPRLR bispecific ADC, dramatically enhances lysosomal
degradation of HER2. Accordingly, bispecific ADCs improve upon T-DM1 efficacy in cells expressing intermediate levels of HER2. These results demonstrate that coupling a tumor-specific ADC target to a rapidly internalizing
protein may be a useful approach to enhance efficacy of ADCs.
9:35 AMX-268 an EpCAM-Targeted T Cell Engager with Best in Class Therapeutic Index
Volker Schellenberger, CEO & President, Discovery, Amunix
AMX-268 is an EpCAM-targeted T cell engager engineered to reduce in vivo on-target but off-tumor toxicity by at least10 fold compared to other T cell engagers. AMX-268 is based on Amunix’ proprietary ProTIA platform,
which combines three targeting modalities: 1) tumor target binding, 2) local activation by tumor associated proteases, 3) Polymer exclusion form healthy tissues (EPR effect). Tumor specific antibodies can be rapidly converted
into ProTIA and results for multiple targets will be shown.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
11:05 Application of DART® Platform to Reverse Checkpoint Blockade and Enhance Immune Effector Function
Ross La Motte-Mohs, PhD, Scientist III, Cell Biology and Immunology, MacroGenics,
Inc.
T cell exhaustion in cancer is associated with the expression of checkpoint molecules, including PD-1, CTLA-4 and LAG-3, that cooperate in inducing loss of immune cell effector function, leading to disease progression. Dual
blockade of checkpoint molecules can overcome limitations associated with single molecule inhibition. Here we present an update on PD-1 x CTLA-4 (MGD019) and PD-1 x LAG-3 (MGD013) DART molecules as dual checkpoint inhibitors
for restoring and/or enhancing T cell effector function.
11:35 PANEL DISCUSSION: Safety and Efficacy of Bispecific Antibodies vs. CAR T
Moderator:
G. Jonah Rainey, PhD, Executive Director, Head of Antibody Research, MabVax Therapeutics
Holdings, Inc.
Panelists:
Carl Uli Bialucha, PhD, Oncology Biotherapeutics, Novartis Institutes for BioMedical Research,
Inc.
Adrian Bot, MD, PhD, Vice President, Translational Sciences, Kite, a Gilead Company
Tara Arvedson, PhD, Director, Oncology Research, Amgen, Inc.
Bob Valamehr, PhD, Vice President, Cancer Immunotherapy, Fate Therapeutics
- Comparison of efficacy: approved and pipeline molecules. What is the best clinical endpoint?
- Costimulation: included as part of the CAR, but what about bispecifics?
- Toxicity: mechanisms of CRS/cytokine storm and ways to prevent and manage them
- On/off target activation: runaway CAR T proliferation, off-target effects, and antigen-independent T-cell activation
12:35 pm End of Advancing Bispecific Antibodies and Combination Therapy to the Clinic